Biomimetic radiation-crosslinked collagen and gelatin as in vitro model to study the physics of tumor progression and medication.

• Applicants: Professor Dr. Stefan Mayr; Professorin Dr. Mareike Zink
• Subject Area: Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics
• Term: since 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 326558614

Cancer constitutes one of the leading causes of death and illness worldwide, and development of effective therapies can be considered among the largest challenges that mankind faces. Despite much progress during the past decades, however, understanding of the underlying physical processes that foster tumor progression and the formation of metastasis are far from complete, and concepts for even more effective therapeutic approaches are highly desirable. The present project addresses both of these challenges of cancer research from a physics perspective, while focusing on the very particular question of crosslinking of collagen and its derivatives. In fact, while it has been established for decades among oncologists that tumors such as mamma carcinomas can be detected by palpation, the relation of crosslinkinginduced extracellular matrix (ECM) stiffening to tumor development, in particular invasive tumor behavior, has only been appreciated recently. In this context collagen I as one of the major components of the ECM in the surrounding of the tumor (in fact, carcinomas) plays a crucial role. Within an interdisciplinary approach, electron irradiation provides us with a tool to systematically address these questions by its capabilities to reagent-free crosslink collagen and build up a biomimetic in vitro matrix. Beyond that, it will enable us to develop a novel type of three dimensional tumor model with realistic 'tunable' mechanical properties based on porous collagen of variable stiffness as ECM model, in which spheroids of malignant cells of different aggressiveness will be incorporated. It will not only allow for identification of parameters for tumor spreading, but, in fact, also serve as in vitro model for chemotherapy. The latter will be in the focus of the second challenge of this project, which focuses on development on a programmable biodegradable gelatin-based con¬trolled release system for chemotherapy. Derived from collagen, gelatin can be similarly crosslinked using electron irradiation, resulting in highly tunable release rates and lifetimes under physiological condition. Assessing this novel controlled release system with the newly developed three dimensional tumor model in terms of delivery characteristics for chemotherapeutics, will complete this project and offer new perspectives to a better understanding how mechanical properties and cellular dynamics influence tumor progression and how temporal chemotherapeutics spreading causes cell death.

• DFG Programme: Research Grants